Triethylamine → 7-Methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carboxylic acid ((S)-1-cyclobutyl-pyrrolidin-2-ylmethyl)-naphthalen-2-ylmethyl-amide

HRID 2220711노트

반응식

HRID 2220711 반응식
C(O[C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][NH:14][CH2:15][C:16]1[CH:25]=[CH:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=1)=O)(C)(C)C.C(N(CC)CC)C.[CH3:33][O:34][C:35]1[C:40]2[O:41][C:42]([CH3:45])([CH3:44])[O:43][C:39]=2[CH:38]=[C:37]([C:46](Cl)=[O:47])[CH:36]=1.[C:49]1(=O)[CH2:52]C[CH2:50]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[CH:6]1([N:8]2[CH2:12][CH2:11][CH2:10][C@H:9]2[CH2:13][N:14]([CH2:15][C:16]2[CH:25]=[CH:24][C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:17]=2)[C:46]([C:37]2[CH:36]=[C:35]([O:34][CH3:33])[C:40]3[O:41][C:42]([CH3:45])([CH3:44])[O:43][C:39]=3[CH:38]=2)=[O:47])[CH2:52][CH2:49][CH2:50]1

참가 물질

7

반응물 5

HCID 8471TriethylamineHCID 14496CyclobutanoneHCID 5049666Sodium triacetoxyborohydrideHCID 59772986(S)-2-{[(Naphthalen-2-ylmethyl)-amino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 714100777-Methoxy-2,2-dimethyl-2H-1,3-benzodioxole-5-carbonyl chloride

생성물 1

HCID 586222137-Methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carboxylic acid ((S)-1-cyclobutyl-pyrrolidin-2-ylmethyl)-naphthalen-2-ylmethyl-amide

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Experimental conditions analogous Example 58, from 0.35 g (1.01 mmol) of (S)-2-{[(naphthalen-2-ylmethyl)-amino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester, 10 mL dichloromethane, 169 μL (1.21 mmol) of triethylamine, and 0.27 g (1.12 mmol) of 7-methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carbonyl chloride. The crude mixture was filtered through silica and the compound was deprotected in 10 mL 10% trifluoroacetic acid/dichloromethane in 1.5 hours. The reaction mixture was treated with aqueous sodium bicarbonate, and extracted with dichloromethane. The crude material was dissolved in 10 mL of dichloromethane, to this mixture was added 0.21 g (3.0 mmol) of cyclobutanone and 0.636 g (3.0 mmol) of sodium triacetoxyborohydride. After overnight the reaction was quenched with aqueous sodium bicarbonate and di-tert-butyl dicarbonate. The organic layer was separated, the residue was purified using flash chromatography (7N ammonia in methanol, 0-3% in dichloromethane), gave 76 mg of off white solid as a free base. LC-MSD, m/z for C31H36N2O4 [M+H]+: 501.7. 1H NMR (400 MHz, CDCl3/HCl): δ 1.7 (s, 6 H), 1.9-2.7 (m, 10 H), 2.8-3.0 (m, 1 H), 3.5-3.7 (m, 1 H), 3.8 (s, 3 H), 3.8-4.0 (m, 4 H), 4.9-5.0 (m, 1 H), 5.2-53 (m, 1 H), 6.7 (s, 1H), 6.8 (s, 1 H), 7.2-7.3 (m, 1H), 7.4-7.5 (m, 2 H), 7.7 (s, 1 H), 7.8-7.9 (m, 3 H), 12.2-12.3 (m, 1 H).

후처리

  1. filtrationThe crude mixture was filtered through silica
  2. additionThe reaction mixture was treated with aqueous sodium bicarbonate
  3. extractionextracted with dichloromethane
  4. dissolutionThe crude material was dissolved in 10 mL of dichloromethane, to this mixture
  5. customAfter overnight the reaction was quenched with aqueous sodium bicarbonate and di-tert-butyl dicarbonate
  6. customThe organic layer was separated
  7. customthe residue was purified
  8. customgave 76 mg of off white solid as a free base

출처 및 근거

ORD 기록
ord-c07e49fcfa41463e8b3644b4d5a64ff6
출처 데이터셋
uspto-grants-2008_08
특허 번호
US07417062B2

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